The long-term objective of the proposed research is to improve our understanding of the mechanisms involved in the control of vascular tone. Fundamental knowledge of the cellular mechanisms which regulate vascular smooth muscle tone is needed for the development o new forms of treatment and drugs directed at vascular disease such as hypertension. The aims of this proposal are to explore the metabolism of arachidonic acid, the precursor of a variety of vasoactive substances, using human and bovine intrapulmonary artery and vein, human and canine saphenous vein and human aortic buttons from the ascending aorta. Radiolabelled arachidonic acid or prostaglandin endoperoxide 14C-PGH2 will be employed as substrates. The substrate will be incubated with rings or microsomes from the vascular segments. The effects of varying the concentrations of enzyme and substrate, time of incubation, pH and temperature will be determined. The effects of cofactors such as glutathione and various inhibitors such as indomethacin on the formation of product of arachidonic acid will be determined. Comparisons of the in vitro arachidonic acid and PGH2 metabolism of artery vs. vein, artery vs. artery and vein vs. vein in different vascular beds in different species will be made. Additionally, the responses of the intact canine saphenous vein to endogenous (ionophore-stimulated) and exogenous arachidonic acid will be determined and correlated with the canine saphenous vein in vitro studies. The unifying goal of this proposal is to improve our knowledge of the regulation of vascular smooth muscle.